Background/Purpose:

A great deal of recent attention has been directed at a possible link between intestinal microbial metabolism and inflammation. Metabolites represent the intermediate products of physiological processes that are influenced by the mechanisms of disease, environment, microbiota, and the digestion and biotransformation of foods and their constituents. Metabolomics captures the global metabolic status of individuals by assaying an extensive set of metabolites simultaneously. This study was undertaken to investigate discriminant metabolites in urine from patients with established rheumatoid arthritis (RA) from healthy individuals and patients with systemic lupus erythematosus (SLE). We further identified the in vivo role of metabolites in the animal arthritis model and human clinical data.

Methods:

Urine samples were collected from 148 established RA patients, 41 SLE patients and 104 healthy participants. Urinary metabolomic profiles were assessed using ¹H-NMR spectroscopy. The relationships between discriminant metabolites and clinical variables were assessed in a large clinical cohort. Collagen-induced arthritis was induced in mice to determine if a choline-rich diet reduces arthritis progression.

Results:

The urinary metabolic fingerprint of patients with established RA differs from that of healthy controls and SLE patients. Metabolites of gut microbiota and diet (trimethylamine-N-oxide; TMAO), and oxidative stress (dimethylamine) were upregulated in patients with RA. Metabolites of mitochondrial dysfunction (citrate and succinate) and metabolic waste products (p-cresol sulfate; p-CS) were downregulated. Urine metabolites were associated with RA disease activity. Particularly, urine levels of TMAO were negatively associated with serum inflammatory markers in patients with RA. Moreover, a more rapid radiographic progression over two years was observed in patients with lower p-CS levels. The in vivo functional study demonstrated that mice fed with 1% choline, a source of TMAO, showed a less severe form of collagen-induced arthritis than those fed with normal diet.

Conclusion:

Patients with RA showed a distinct urinary metabolomics pattern. Urinary TMAO and p-CS can serve an indicative of inflammation or accelerated radiographic progression of RA. A choline-rich diet reduces experimentally-induced arthritis, suggesting that interaction of diet with intestinal microbiota contributes to the phenotype of RA.

Acknowledgement:

This work was supported by grants from the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2015R1A3A2032927 and 2016R1D1A1A02937326).

« Back to 2018 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/distinct-metabolic-profile-in-the-urine-of-rheumatoid-arthritis-patientsa-possible-link-to-arthritis-phenotypes/